3-139935427-G-T

Variant names:

• chr3-139935427-G-T
• NM_022131.3:c.53G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022131.3(CLSTN2):​c.53G>T​(p.Gly18Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLSTN2 NM_022131.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.35
• Publications: 0 publications found

Genes affected

CLSTN2 (HGNC:17448): (calsyntenin 2) Predicted to enable calcium ion binding activity. Predicted to be involved in positive regulation of synapse assembly and positive regulation of synaptic transmission. Predicted to be located in postsynaptic density. Predicted to be active in cell surface; glutamatergic synapse; and postsynaptic membrane. Predicted to be integral component of postsynaptic density membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022131.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLSTN2	NM_022131.3	MANE Select	c.53G>T	p.Gly18Val	missense	Exon 1 of 17	NP_071414.2	Q9H4D0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLSTN2	ENST00000458420.7	TSL:1 MANE Select	c.53G>T	p.Gly18Val	missense	Exon 1 of 17	ENSP00000402460.2	Q9H4D0
	CLSTN2	ENST00000511524.1	TSL:2	n.241G>T		non_coding_transcript_exon	Exon 1 of 11

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1079306 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 509668

African (AFR) AF: 0.00 AC: 0 AN: 22910

American (AMR) AF: 0.00 AC: 0 AN: 8376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14320

East Asian (EAS) AF: 0.00 AC: 0 AN: 26486

South Asian (SAS) AF: 0.00 AC: 0 AN: 19492

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 919466

Other (OTH) AF: 0.00 AC: 0 AN: 43620

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.081	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.49	T
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.3
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	0.23	N
REVEL	Benign	0.18
Sift	Benign	0.28	T
Sift4G	Benign	0.20	T
Polyphen		1.0	D
Vest4		0.48
MutPred		0.49		Gain of sheet (P = 0.0061)
MVP		0.76
MPC		0.78
ClinPred		0.81	D
GERP RS		4.3
PromoterAI		0.026	Neutral
Varity_R		0.21
gMVP		0.32
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr3-139654269;